The objectives of the proposed research are to characterize the mechanisms by which steroid D-ring glucuronides inhibit bile flow and bile acid secretion. The effect of the cholestatic glucuronides on Na+K+-ATPase activity and the binding of bile acids will be investigated in vitro in canalicular enriched fraction of plasma membranes to determine if there is a correlation with in vivo inhibition of bile acid independent and bile acid dependent flow respectively. The effects of pregnancy and chronic estrogen treatment on the metabolism and biliary excretion of drugs and model compounds will also be investigated. The model systems to be used are isolated rat hepatic plasma membranes, the isolated perfused rat liver and in vivo in the rat.